TBC

Nguyen et al.
BMC Infectious Diseases 2014, 14:617

http://www.biomedcentral.com/1471-2334/14/617
RESEARCH ARTICLE
Open Access
Tuberculosis care for pregnant women: a

systematic review
Hang Thanh Nguyen1*, Chiara Pandolfini1, Peter Chiodini2 and Maurizio Bonati1
Abstract
Background: Tuberculosis (TB) during pregnancy may lead to severe consequences affecting both mother and
child. Prenatal care could be a very good opportunity for TB care, especially for women who have limited access
to health services. The aim of this review was to gather and evaluate studies on TB care for pregnant women.
Methods: We used a combination of the terms tuberculosis and pregnancy, limited to human, to search for
published articles. Studies reflecting original data and focusing on TB care for pregnant women were included.
All references retrieved were collected using the Reference Manager software (Version 11).
Results: Thirty five studies were selected for review and their data showed that diagnosis was often delayed
because TB symptoms during pregnancy were not typical. TB prophylaxis and anti-TB therapy appeared to be safe
and effective for pregnant women and their babies when suitable follow up and early initiation were present, but
the compliance rate to TB prophylaxis is still low due to lack of follow up and referral services. TB care practices in
the reviewed studies were in line in principle with the WHO International Standards for Tuberculosis Care (ISTC).
Conclusions: Integration of TB care within prenatal care would improve TB diagnosis and treatment for pregnant
women. To improve the quality of TB care, it is necessary to develop national level guidelines based on the ISTC
with detailed guidelines for pregnant women.
Keywords: Delivery of health care, Pregnancy, Tuberculosis, Women
Background
According to the World Health Organization (WHO),
every year about 700,000 women die of tuberculosis (TB)
and over three million contract the disease [1]. TB is the
third leading cause of death among women aged 1544. TB
can cause infertility and contributes to poor reproductive
health outcomes [2,3].
When pregnant women contract TB, the disease is more
difficult to diagnose because TB symptoms such as fatigue,
shortness of breath, sweating, tiredness, cough, and mild
fever are similar to physiological symptoms of pregnancy.
Untreated TB or TB treated late may lead to severe consequences affecting both mother and child [4,5]. Pregnant
women with pulmonary TB who are treated appropriately
do not have increased rates of maternal or neonatal complications, while without treatment, TB can lead to
* Correspondence: hang.nguyen@marionegri.it
1
Department of Public Health, Laboratory of Maternal and Child Health,
IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Via G. La Masa 19,
Milan, Italy
Full list of author information is available at the end of the article
increased neonatal morbidity, low birth weight, prematurity, and increased pregnancy complications, including
four-fold increases in maternal morbidity due to higher
rates of abortion, post partum haemorrhage, labour difficulties, and pre-eclampsia [5]. Prenatal care could be a
very good opportunity for TB screening and diagnosis and
for following up TB care, especially for women who have
limited access to health services, such as migrants or
women of limited social/economic status, who only approach medical services when pregnant [4,5].
The WHO Guidelines for Treatment of Tuberculosis
provide recommendations for TB care and recommend the
integration of TB care within both prenatal care procedures
and the Preventing Mother to Child Transmission of HIV
Program (PMTCT) in order to utilise existing health
resources and systems to improve accessibility and effectiveness of TB care for pregnant women and prevent the
mother to child transmission of TB [6].
2014 Nguyen et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.
Nguyen et al. BMC Infectious Diseases 2014, 14:617

Page 2 of 10
Regardless of the importance of TB care in the prenatal

period, however, only a modest number of articles addressing TB in pregnant women have been published. Some
major controversial issues in TB care during pregnancy
remain that require further research, such as the safety,
reliability, and feasibility of TB screening methods used
in the prenatal period [7], drug therapy for pregnant MDR
women [8], and delay of treatment until the post partum
period in case of latent tuberculosis infection (LTBI) [9].
LTBI is a condition in which a person is infected with
Mycobacterium tuberculosis, but does not currently have
active tuberculosis disease.
This systematic review aimed to gather and evaluate
evidence based studies on TB care in pregnancy, with
consideration of WHO standard guidelines for TB care,
in order to recommend better practices to improve
TB care for pregnant women. For studies on TB care
in pregnancy the authors intended those addressing
screening/diagnosis, prevention, treatment, or followup/supervision/counselling activities/services for women
in pregnancy.
Methods
The following databases were searched for articles in English, published in any year up to December 31, 2012: MEDLINE (indexes articles dating back to 1946), EMBASE
(1973), the Cochrane Library (various), and www.clinicaltrials.gov (2000). The search strategies involved 1. using the
MeSH terms tuberculosis and pregnancy, limited to
Identification
human; 2. the terms tuberc* and pregnan* as free text

within articles indexed in the last 90 days, limited to human; 3. combining the results of MeSH tuberculosis and
free text tuberc*; 4. combining the results of MeSH pregnancy and free text pregnan*; 5. combining the results of
steps 3 and 4 (pregnancy AND tuberculosis, limited to
Human). The syntax was adjusted for the specific databases. Reference lists were then searched for potentially
relevant articles.
Inclusion criteria
Studies reflecting original data and focusing on TB care

(screening, diagnosis, treatment, and follow up) in pregnant women.
Exclusion criteria
Articles were excluded if: 1. The target group was NOT

pregnant women, 2. TB was mentioned, but NOT TB care
(i.e. TB as a complication of other diseases, as part of a
study on infectious diseases, etc.); 3. Original data was not
included 4. They were NOT studies (letters, presentations,
conference documents, case reports).
Figure 1 summarizes the selection process for review articles with detailed number of articles in each step.
Data extraction and assessment
All references retrieved were collected and analysed using

the Reference Manager (Version 11) program. All identified
abstracts were read for their applicability to inclusion and
Total articles retrieved 2638

(Embase 1162, Medline 1419,
Cochrane Library 57,
Clinicaltrials website 0)
Duplicates: 218
No authors and/or no abstracts 1077
Screening
Potentially appropriate
articles to be evaluated
1343
Total article abstracts to be

reviewed 670
Editorials, letters, comments,

conference abstracts/papers, notes,
guidelines, reviews 673
Not pertinent 567

Eligibility
Article content to be
reviewed in detail 113
Case reports 78
Included
Figure 1 PRISMA Flow diagram of search strategy.
Studies 35

exclusion criteria by two co-reviewers and discrepancies

were resolved by a third reviewer. Potentially relevant
articles were obtained and examined, and the quality of selected studies was assessed by two evaluators using the
checklists from the National Institute for Health and
Clinical Excellence (NICE)s manual for developing public
health guidance [10] (See Additional file 1). Each study was
evaluated by the appropriate NICE checklist depends on
study type. The quality evaluation took into consideration
the studies internal and external validity. According to
NICE guidelines, a study was rated good quality (++) if it
fulfilled all or most of criteria in the check list, medium
quality if it fulfilled some (+), and low quality if few or no
criteria were fulfilled () [10]. Inter-reviewer reliability was
measured using Cohens Kappa statistics. Discrepancies
were addressed by a third reviewer. MS Excel software was
used to process data from the selected studies.
Details of ethics approval
This is a systematic review of previously published data

and therefore does not require ethical approval.
Results
Summary of included studies
Thirty five studies were selected for detailed review.

Good inter-rater agreement on the quality assessment of
the studies was found (K = 0.70). There were 6 studies
with good quality (++), 21 with medium quality (+), and
8 with low quality (). The reasons to include studies
with low quality is the limited number of studies in selected topics and one of the purpose of this review is to
have an overall evaluation on the situation of research
on TB care for pregnant women.
Table 1 shows the characteristics of the reviewed studies
and the quality evaluation scores. Concerning the study
types, there were 14 cohort studies, 8 before and after studies, 6 cross sectional studies, 4 case control studies, 2 controlled trials, and 1 qualitative study.
Concerning the topics addressed, some studies addressed
multiple topics: 8 studies covered 2 topics and 1 study covered 3. The topic of TB diagnosis/screening was presented
in 21 studies, 14 studies addressed TB treatment (including
4 on MDR treatment), 2 studies were on TB prevention,
specifically on LTBI prophylaxis, and 3 studies were on the
follow-up of womens compliance to the TB prophylaxis
therapy. All studies were published after 1975, with a
majority (26/35) published after 1999. Data originated from
16 different countries. Fifteen studies were carried out in
resource-rich countries: US (11 studies), UK (3), and the
Netherlands (1), while 20 were carried out in resourcelimited countries: South Africa (6 studies), India (3), and
the remaining countries had 1 each. One group of researchers in South Africa conducted 3 studies [22,32,44],
other studies were all conducted by different groups of
Page 3 of 10
researchers. In all, 81093 people were enrolled in these

studies, 37404 of whom in the study group (pregnant
women with TB) and 43689 in the controlled/comparison
groups (pregnant women without TB or/and non-pregnant
women with TB). The large total was mostly due to one
population based study involving 61016 people [14].
TB diagnosis and screening for pregnant women
The procedures for TB screening and diagnosis for pregnant women described in the reviewed studies include the
tuberculin sensitivity test (TST/PPD) followed by the sputum test (Acid-fast bacillus - AFB) and the shielded chest
X-ray [18,19,23,24,30]. The AFB smear test appears to
have low sensitivity in pregnant women [18,19,30], but is
still used in low resource settings as part of the procedure
for diagnosing active TB due to its low cost and simple
technique [13,30]. AFB culture was used as a confirmation
of diagnosis, but is time consuming and not available in
low resource settings [13,23]. Another technique, fluorescence microscopy, was recommended as a substitute for
AFB culture because it is cheaper [13]. This procedure is
for pulmonary TB cases and cannot identify extra pulmonary TB without additional tests and presence of physical TB symptoms. A clinical examination comprising a
questionnaire tracking TB history and detecting TB clinical symptoms was also used and was proven to increase
reliability of TB screening and diagnosis when combined
with paraclinical tests [13,23,27,30,41]. Some authors recommended not using chest X-ray for pregnant women if
there were no clinical symptoms of TB [30].
TST is used widely as the first step in TB screening
and diagnosis and to identify LTBI [18]. Studies showed
that pregnancy does not affect the sensitivity of this test
[20], but its result can be affected by HIV infection or
any situation that severely weakens the immune system
(such as disseminated TB), as these could lead to false
negative results [21,30,45]. BCG vaccination can also
lead to TST positive results in healthy women [11,28].
In a high HIV prevalence setting, other tests and clinical
symptoms should therefore be taken into account in
diagnosing TB [41] and the TST and anergy skin tests
(the latter is used to evaluate whether the immune system is functioning properly or not and can indicate
whether the results of the other skin test are reliable) are
recommended as a TB screening method in the prenatal
care procedures [31]. In populations in which the majority of people are BCG vaccinated or their vaccination
status is uncertain, TST is discouraged and IGRA is recommended for TB screening and diagnosis [11,28].
Concerning the IGRA test, one study in Kenya compared results of this test with the TST in screening for
TB and showed the advantage of the IGRA test over
TST in TB screening and diagnosis for HIV positive
pregnant women, since its sensitivity is not affected by
No. Authors/Year published Year data Study type

(reference)
collected
Topic
No. of cases
Length of study
Country
Quality score*
(from high to low)
Worjoloh et al./2011 [11]
5/2009
3/2010
Cross sectional
Screening
220
10 months
US
++
Sangala et al./2006 [12]
2006
Qualitative
Screening
40 (15 pregnant, 15 non pregnant, 10

antenatal care providers)
N/A
Malawi
++
Gounder et al./2011 [13]
12/20087/2009
Cross sectional
Screening,
prevention
3963
7 months
South
Africa
++
Czeizel et al./2001 [14]
1980-1996 Case control
Treatment
61016 (38151 controls and 22865 cases)
16 years
Hungary
++
Tripathy et al./2003 [15]
1986-2001 Prospective cohort study
Treatment
213 (111 pregnant with TB, 51 pregnant

without TB, 51 non pregnant with TB)
15 years
India
++
Jana et al./1999 [16]
Treatment

without TB)
10 years
India
++
Figueroa-Damian et al./
1998 [17]
Treatment

without TB)
5 years
Mexico
Carter et al. /1994 [18]
1987-1991 Retrospective cohort study
Diagnosis
22 (7 pregnant, 15 nonpregnant)
4 years
US
Doveren et al./1998 [19]
Diagnosis
14 (5 pregnant, 9 non pregnant)
6 years
Netherlands +
Present et al./1975 [20]
1975
Non-randomized controlled trial
Diagnosis
326 (167 pregnant, 226 nonpregnant)
1 year
US
11
Jonnalagadda et al./2010
[21]
1997 2005
Prospective cohort study
Diagnosis
333
8 years
Kenya
12
Khan et al./2001 [22]
1996-1998 Prospective study cohort 1997

1998, retrospective cohort study
1996
Diagnosis
101
3 years
South
Africa
13
Knight et al./2009 [23]
2005-2006 Cross sectional
Diagnosis
33
1 year
UK
14
Kothari et al./2006 [24]
1/199712/2001
Before and after study
Diagnosis,
treatment,
follow-up
32
5 year
UK
15
Kwara et al./2008 [25]
2003
Retrospective cohort study
Follow up
845 (97 pregnant women)
1 year
US
16
Cruz et al./2005 [26]
2000
Follow-up
425
1 year
US
17
Kali et al./2006 [27]
6/200310/2003
Cross sectional
Screening
370
4 months
South
Africa
18
Sepulveda et al./1995
[28]
Screening
840
3 years
Chile
19
Meints et al./2010 [29]
2003-2006 Cross sectional
Screening
1767
4 years
US
20
Sheriff et al./2010 [30]
6/2008-8/
2008)
Screening
286
2 months
Tanzania
21
Mofenson et al./1995 [31] 9/1989 -3/ Prospective cohort study

1993
Screening,
diagnosis
183 (65 pregnant and 118 nonpregnant)
3.5 years
US and
+
Puerto Rico
22
Pillay et al./2001 [32]
Screening,
diagnosis
146
2 years
South
Africa
Cross sectional
Page 4 of 10
9
10

Table 1 Characteristics of reviewed studies and quality evaluation results, sorted by quality evaluation score
23
Margono et al./1994 [33]
1985-1992 Before and after study
Screening,
diagnosis,
treatment
16
7 years
US
24
Lighter-Fisher et al./2012
[34]
2012
Non-randomized controlled trial
Screening,
diagnosis
280 (140 pregnant women, 140 non

pregnant women)
N/A
US
25
Donald et al./1991 [35]
1991
Treatment
30 children with mothers who received N/A

streptomycin injection during pregnancy
South
Africa
26
Palacios et al./2009 [36]
1996
-2005
Treatment
(drug resistant)
38
10 years
Peru
27
Tabarsi et al./2011 [37]
Treatment
(drug resistant)
6 years
Iran
28
Cheng et al./2003 [38]
2002
Diagnosis,
treatment
29
Done in 2002 with

article search 19662002
Hong Kong, China
29
Franks et al./1989 [39]
Prevention
7629 (3681 pregnant, 3948 nonpregnant)
18 months
US
30
Sackoff et al./2006 [40]
Prevention,
follow-up
730
1 year
US
31
Gupta et al./2011 [41]
Screening
799
5 years
India
32
Keskin et al./2008 [42]
Treatment
5 years
Turkey
33
De Oliveira et al./2011
[43]
Treatment
(drug resistant)
13 years
Brazil
34
Khan et al./2007 [44]
Treatment
(drug resistant)
5 years
South
Africa
35
Llewelyn et al./2000 [45]
12/19955/1998
Diagnosis,
treatment
13
30 months
UK
Prospective cohort study

Table 1 Characteristics of reviewed studies and quality evaluation results, sorted by quality evaluation score (Continued)
*(++): High quality; (+) Medium quality; () Low quality.
Page 5 of 10

HIV infection [21]. Two studies proved the value of

IGRA in detecting LTBI in pregnant women, since the
results of this test were not affected by BCG vaccination,
thus avoiding the TST false positive result and the unnecessary, consequent INH prophylaxis [11,21].
Prevention
TB prevention includes BCG vaccination in childhood

and INH prophylaxis for LTBI positive people. There were
2 studies on TB prevention and both were on INH
prophylaxis for LTBI pregnant women. Both were conducted in the US with pregnant women of foreign origin
and LTBI was diagnosed by TST [39,40]. One study [40]
showed a low completion rate of INH therapy ( 9.3% ) and
the other showed a high risk of INH toxic hepatitis, with
pregnant women having a 2.5 fold greater risk of INH
hepatitis than non-pregnant women (but this result was
not statistically significant due to the small number of
women) [39]. The 2 studies found that the main reason
for this discouraging result was a lack of follow up and referral services for pregnant women undergoing INH
prophylaxis [39,40].
Treatment
There were 375 pregnant women with TB in the 14

studies on TB treatment. Treatment outcome was generally positive, with 332/375 women cured (confirmed by
AFB culture conversion). In terms of mortality, 25
women died during treatment, 11 of whom died due to
meningitis TB, 11 due to MDR-TB, 2 due to acute respiratory distress syndrome (ARDS), and 1 due to a nonTB related reason (massive pulmonary embolism). Other
than mortality, the negative treatment outcomes included 4 treatment failures, 4 cases of residual functional
deficit, 7 treatment terminations due to adverse drug effects, and 3 cases of treatment abandonment.
In terms of pregnancy outcome, only 11 women chose
to terminate the pregnancy when they discovered their
TB situation, while the others continued the pregnancy
and underwent TB therapy. Among the pregnant women
undergoing TB therapy, 332 women gave birth, 1 had a
therapeutic abortion, 3 had miscarriages, 3 had stillborns, and 25 died. Concerning the 332 cases of mothers
who gave birth, 4 infants died shortly after birth due to
pneumonia and prematurity, 2 were HIV positive, 1 had
active TB, 2 had LTBI, 50 were low birth weight, and 7
had growth restriction. Studies also showed that HIV infected women were more likely to choose pregnancy termination and had higher mortality and morbidity rates,
even with intensive TB treatment combined with HIV
treatment [33,44].
The first line drugs used for pregnant women in the
studies included INH, ethambutol (ETB), rifampicin (RIF),
and, in some cases of extra pulmonary TB, pyrazinamid
Page 6 of 10
(PZA) [15,19,33,45]. In the MDR cases, the second line

drugs, including drugs of the amino glycosides group,
fluoroquinolone, thioamides, cycloserines, and terizidone,
were used in combination with effective first line drugs,
and the treatment regime depended on the drug resistance
situation of the individual cases [36,37,43,44].
Regarding effectiveness and safety of anti-TB drugs,
results of the reviewed studies showed no significant
association between child abnormality and mothers
exposure to anti-TB drugs, both for 1st and 2nd line antiTB drugs during pregnancy [14,15,37,43,44]. Other significant adverse effects were recorded in a very small
number of pregnant women (2 cases of drug induced
hepatitis, 2 of PZA allergy, 2 of sensorineural deafness,
and 1 of severe nausea and jaundice) and led to termination of therapy without mortality [24,44]. Streptomycin
(SM) was not used in any studies because of its potential
risk of deafness in babies. However, a retrospective study
was conducted, checking the hearing capacity of 30 children whose mothers received SM injection during pregnancy, and found no significant effect, with only one
case of deafness possibly linked to the mothers use of
SM. Authors of this study recommend only using SM
after the 2nd trimester if really necessary [35].
There were 4 studies with 55 pregnant women on MDR
treatment. Unlike other studies, in these TB was detected
in all the women before pregnancy. More specifically, 48/
55 of the women had been diagnosed with MDR TB and
had already taken 2nd line anti-TB drugs before getting
pregnant, while 7/55 were diagnosed MDR TB and started
therapy during pregnancy [36,37,43,44]. After being counselled by clinicians, only 6/55 women chose abortion,
while the rest decided to continue the pregnancy and
undergo MDR therapy [37,44]. Eleven women died (8 died
during treatment and 3 died after completing treatment
for unknown reasons). There was one stillbirth and one
child died prematurely due to pneumonia. One woman
and her child were lost to follow up. One woman had to
terminate treatment due to hepatitis. Other cases were
treated successfully. The results of the studies showed
that, with an attentive follow-up and appropriate therapy,
MDR-TB pregnant women can be cured and have a positive maternal outcome, and should therefore be given the
option to continue with a pregnancy [36,37,44]. The
results also showed that a delay in, or default, MDR treatment were the main causes of mortality and morbidity for
mothers and babies [36,43,44].
Follow-up
Follow-up actions for TB therapy include checking for a

womans drug consumption, clinical symptoms of antiTB drug adverse effects, and liver function tests. Good
compliance with TB treatment in pregnant women led
to better maternal outcome and TB recovery rate. These

Page 7 of 10
studies showed that adequate health services and directly

observed therapy (DOT) could greatly contribute to
womens compliance, and, therefore, to treatment success [36,45].
There were 3 studies on follow-up of TB therapy for
pregnant women and all were on INH prophylaxis. Pregnant women with LTBI were offered 6 months of prophylaxis with INH. The compliance rate was low, possibly due
to the womens concern about hepatitis and other adverse
effects [25,40], and the lack of referral services for treatment evaluation and action from health care providers to
ensure compliance [40]. Compared to the general population, pregnant women were less likely to initiate the INH
prophylaxis 52.1% vs 14.7% [25]. In all 3 studies, the completion rate among pregnant women was very low (14.7%,
9.3%, and 21.2%) [25,26,40]. All studies recommended that
health care providers implement better follow-up strategies
to increase patient compliance in the prenatal and postpartum periods, ensure follow-up of drug adverse effects,
and not dispense INH quantities covering more than
30 days of treatment at each visit.
TB culture mandatory since it is the most reliable standard for confirming TB infection and treatment effectiveness, and for revising the therapy in case of lack of success
[15,33]. Treatment of extra PTB had a less positive prognosis than PTB due to greater difficulty in diagnosis and
treatment [16,38]. If women are diagnosed and treated
with anti-TB early, however, the maternal outcome can be
positive [16,24,33,45].
The low LTBI treatment completion rates raised concerns about LTBI prophylaxis during pregnancy. Follow
up actions for LTBI in reviewed studies required women
go to the health clinics for check-ups and to obtain more
medication, but no onsite enforcement in the community/family, such as DOT or visits, was provided to
reinforce patient compliance [25,26,40]. These studies
showed the importance of health services in follow-up,
since pregnant women who receive health care from the
same clinician before and after delivery, who have insurance, or who receive continuous care from clinics outside hospitals were more likely to complete the therapy
[25,26].
Discussion
Strengths and limitations
Main findings
The strength of the review is that all aspects of TB care in

different settings were considered and reviewed and that
the authors could therefore use the WHO ISTC as a
standard to which to compare TB care practices. However,
the review has some limitations. The studies reviewed
were of limited quality and covered multiple aspects of TB
care, no intensive analysis for each aspect could therefore
be performed. There was a limited number of populationbased studies, since most were conducted in a single
clinic. Results are therefore not solid enough to be applicable to a larger population. Another limitation was that
few studies had control groups; some used comparison
groups that were not fully comparable with the study
group [16-18,20,25,28,31,39]. Furthermore, the study designs were weak, since no randomised controlled trials
were present. Only one qualitative study was found, and
with a disease related to socio-economic status and poverty as is TB, additional qualitative studies would have
been useful in identifying attitudes, behaviours, challenges,
and opportunities for shaping effective interventions/
policies for better care for TB patients. A more general
limitation is that the differing resources available between
different countries make it difficult to generalise the
conclusions.
In resource-rich countries, pregnant women with high TB

prevalence are migrants and people of foreign origin
[11,18,23,24,28,45], while in resource-limited countries,
HIV infected pregnant women are the group with high TB
prevalence and mortality [13,22,27,32,41].
The major problem concerning TB diagnosis for pregnant women is the delay in diagnosis, with a median
delay time, defined as the duration from symptom onset
to confirmation of diagnosis, ranging from 7 days to
6 months. The main reasons for this delay are that
women seek health services and prenatal care at a late
stage of their pregnancy and that TB during pregnancy
is asymptomatic or has nonspecific symptoms, especially
in cases of extra pulmonary TB [18,23,38,45]. Compared
to non-pregnant women, pregnant women were more
likely to be diagnosed with TB via routine screening (as
part of prenatal care) [30]. In HIV infected people, the
difficulty in diagnosis is even greater since the weak immune reaction may cause false negative TST and make
early TB symptoms unclear [21,32]. Thus, all studies recommended the integration of TB screening in prenatal
care procedures for high risk groups.
In terms of treatment, studies have shown the importance of starting treatment as soon as possible, even before
TB culture results, to revert the negative impact of TB on
mothers and babies [17,24,33,45]. Early treatment of TB
(1st and 2nd trimester) led to a maternal outcome comparable to that of non-TB infected pregnant women, and to a
much better outcome than that of women who received
late treatment [17]. Authors also recommended making
Interpretation
According to the WHO guidelines, the ISTC applies to the

general population, with only a notion on avoiding using
streptomycin in treatment during pregnancy [6,46]. In
principle, TB care practices in the reviewed studies were
consistent with the ISTC. However, in resource-limited

countries some standards could not be put into practice

(See Additional file 2).
Since the WHO guidelines focus on resource-limited
countries with high TB prevalence, these may not be entirely appropriate for resource-rich countries. The comparison with the ISTC also revealed that, although TB diagnosis
and treatment facilities in resource-rich countries are better,
the role of counselling and support/supervision has not
drawn enough attention on the part of health care
providers and researchers in such countries, albeit WHO
considers these as important standards to ensure patient
compliance to TB treatment.
Conclusions
Review results have proven both the importance of TB care
in reducing TB mortality and morbidity for women and
their babies, and the feasibility of TB control interventions,
even in limited resource settings. Several recommendations
to improve the quality of TB care for pregnant women can
be made based on the results of the review:
TB care for pregnant women should utilise available
health system resources, especially the antenatal care
programs, and should include the patient-centred approach
in counselling, supervision, and support as well as a wellmanaged, nation-wide method of treatment record keeping
to ensure patients compliance to TB treatment.
Concerning the target of TB care, in resource-rich countries screening interventions should focus on the foreign
origin population, while in resource-limited countries interventions should focus on areas with low socio-economic
status and high prevalence of HIV infection.
Raising doctors awareness on TB is fundamental.
When visiting women with unclear symptoms such as
fever, doctors should consider TB and investigate the
womans history and prescribe TB tests in order not to
delay diagnosis and to avoid severe consequences.
Concerning TB diagnostic tests, considering the low
sensitivity of the AFB smear test in diagnosis for pregnant women and the advantage of the IGRA test over
the AFB smear test, IGRA is recommended in diagnosis
and screening if possible. Further studies are therefore
needed on its specificity and reliability, and on its applicability to a wider population.
Additional studies on TB therapies for pregnant women
should be performed, given their scarcity, especially for
MDR TB.
Before deciding to start the TB preventive therapy, BCG
vaccination status should be confirmed, and during
therapy, the test to detect INH adverse effects should be
conducted regularly. More active involvement of health
care providers in following up womens compliance could
improve the low completion rate of therapy.
Information on individual/family history of TB infection, BCG vaccination, and past treatment, for example,
Page 8 of 10
were hardly collected. Collecting such information from

patients during the first visit and giving this step high
priority could help to improve diagnosis and treatment.
Additional studies, both qualitative and quantitative, and
clinical and community-based, need to be performed and
should not only address the quality of TB care provided by
service providers, but also the behaviours and attitudes of
individuals and communities in approaching and using
available health services and the barriers faced in accessing
and complying with TB treatment. It would be especially
important to address issues such as carrying out TB
cultures, for which patients then have to return to the clinic
for the results, and following up for INH toxicity, since in
poor resource settings travelling, for example, is a significant barrier for patients. National TB care guidelines based
on the ISTC with detailed guidelines for TB care for
pregnant women are necessary. Improvement in TB care
for pregnant women will contribute significantly to achieving the Millennium Development Goal target of halting TB
by 2015 and beginning to reverse the incidence of TB [47].
Additional files
Additional file 1: NICE checklists.
Additional file 2: Comparison of ISTC and TB care practices.
Abbreviations
AFB: Acid-fast bacillus; ARDS: Acute respiratory distress syndrome;
DOT: Directly observed treatment; DR: Drug resistant; HIV: Human
immunodeficiency virus; IGRA: Interferon gamma release assay;
ISTC: International standards for tuberculosis care; LTBI: Latent tuberculosis
infection; MDR-TB: Multidrug resistant tuberculosis; PTB: Pulmonary
tuberculosis; TB: Tuberculosis; TST: Tuberculin sensitivity test; WHO: World
health organization; XDR-TB: Extensively drug resistant tuberculosis.
Competing interests
The authors declare that they have no competing interests.
Authors contributions
THN, CP and MB participated in the formulation of the methodology for this
review. THN performed the literature search and reviewed all abstracts and
full text articles with assistance from CP and MB. THN wrote the first draft of
the manuscript and CP, PC and MB assisted in the writing and editing of the
manuscript. All authors read and approved the final manuscript.
Authors information
THN is doctoral fellow, CP is researcher, and MB is Head of the Laboratory
for Mother and Child Health, Department of Public Health, IRCCS - Istituto di
Ricerche Farmacologiche Mario Negri, Milan, Italy. PC is professor in the
Department of Clinical Parasitology, University College London Hospitals
NHS Foundation Trust, London, UK.
Acknowledgements
This work has been supported by the EC within the 7th Framework Programme
under the COHEMI project - grant agreement no. FP7GA-261495.
Author details
1
Department of Public Health, Laboratory of Maternal and Child Health,
IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Via G. La Masa 19,
Milan, Italy. 2Department of Clinical Parasitology, University College London
Hospitals NHS Foundation Trust, London, UK.

Received: 13 May 2014 Accepted: 6 November 2014
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doi:10.1186/s12879-014-0617-x
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Nguyen et al.

BMC Infectious Diseases 2014, 14:617

Tuberculosis care for pregnant women: a

Nguyen et al. BMC Infectious Diseases 2014, 14:617

Regardless of the importance of TB care in the prenatal

human; 2. the terms tuberc* and pregnan* as free text

Studies reflecting original data and focusing on TB care

Articles were excluded if: 1. The target group was NOT

All references retrieved were collected and analysed using

Total articles retrieved 2638

Total article abstracts to be

Editorials, letters, comments,

Not pertinent 567

Figure 1 PRISMA Flow diagram of search strategy.

Nguyen et al. BMC Infectious Diseases 2014, 14:617

exclusion criteria by two co-reviewers and discrepancies

This is a systematic review of previously published data

Thirty five studies were selected for detailed review.

researchers. In all, 81093 people were enrolled in these

No. Authors/Year published Year data Study type

Worjoloh et al./2011 [11]

Sangala et al./2006 [12]

40 (15 pregnant, 15 non pregnant, 10

Gounder et al./2011 [13]

Czeizel et al./2001 [14]

1980-1996 Case control

61016 (38151 controls and 22865 cases)

Tripathy et al./2003 [15]

1986-2001 Prospective cohort study

213 (111 pregnant with TB, 51 pregnant

Jana et al./1999 [16]

1983-1993 Case control

165 (33 pregnant with TB, 132 pregnant

1990-1995 Case control

100 (25 pregnant with TB, 75 pregnant

Carter et al. /1994 [18]

1987-1991 Retrospective cohort study

Doveren et al./1998 [19]

1990-1996 Retrospective cohort study

14 (5 pregnant, 9 non pregnant)

Present et al./1975 [20]

Non-randomized controlled trial

326 (167 pregnant, 226 non- pregnant)

Prospective cohort study

Khan et al./2001 [22]

1996-1998 Prospective study cohort 1997

Knight et al./2009 [23]

2005-2006 Cross sectional

Kothari et al./2006 [24]

Before and after study

Kwara et al./2008 [25]

Retrospective cohort study

845 (97 pregnant women)

Cruz et al./2005 [26]

Retrospective cohort study

Kali et al./2006 [27]

1991-1994 Prospective cohort study

Meints et al./2010 [29]

2003-2006 Cross sectional

Sheriff et al./2010 [30]

Mofenson et al./1995 [31] 9/1989 -3/ Prospective cohort study

183 (65 pregnant and 118 nonpregnant)

Pillay et al./2001 [32]